About: A pH-dependent switch mediates conformational masking of SARS-CoV-2 spike

Facets (new session)
Description
Metadata
Settings
- owl:sameAs
- Inference Rule:

About: A pH-dependent switch mediates conformational masking of SARS-CoV-2 spike Goto Sponge NotDistinct Permalink

An Entity of Type : schema:ScholarlyArticle, within Data Space : wasabi.inria.fr associated with source document(s)

Attributes	Values
type	Academic Article research paper schema:ScholarlyArticle
isDefinedBy	Covid-on-the-Web dataset
title	A pH-dependent switch mediates conformational masking of SARS-CoV-2 spike
Creator	Wang, Pengfei Shi, Wei Zhou, Tongqing Tsybovsky, Yaroslav Schön, Arne Chuang, Gwo-Yu Sastry, Mallika Zhang, Baoshan Mascola, John Teng, I-Ting Kwong, Peter Boyington, Jeffrey Ho, David Olia, Adam Cerutti, Gabriele Gorman, Jason Rapp, Micah Shapiro, Lawrence Stephens, Tyler Wang, Shuishu Katsamba, Phinikoula Nazzari, Alexandra Stuckey, Jonathan Sampson, M
source	BioRxiv; Medline; PMC
abstract	SARS-CoV-2 has emerged as a global pathogen(1,2), sparking urgent vaccine development efforts with the trimeric spike(3,4). However, the inability of antibodies like CR3022(5), which binds a cryptic spike epitope with nanomolar affinity(6), to neutralize virus, suggests a spike-based means of neutralization escape. Here, we show the SARS-CoV-2 spike to have 10% the unfolding enthalpy of a globular protein at physiological pH, where it is recognized by antibodies like CR3022, and up to 10-times more unfolding enthalpy at endosomal pH, where it sheds such antibodies, suggesting that the spike evades potentially neutralizing antibody through a pH-dependent mechanism of conformational masking. To understand the compatibility of this mechanism with ACE2-receptor interactions, we carried out binding measurements and determined cryo-EM structures of the spike recognizing up to three ACE2 molecules at both physiological and endosomal pH. In the absence of ACE2, cryo-EM analyses indicated lower pH to reduce conformational heterogeneity. Single-receptor binding domain (RBD)-up conformations dominated at pH 5.5, resolving into a locked all-down conformation at lower pH through lowering of RBD and refolding of a pH-dependent switch. Notably, the emerging Asp614Gly strain(7) partially destabilizes the switch that locks RBD down, thereby enhancing functional interactions with ACE2 while reducing evasion by conformational masking.
has issue date	2020-07-04(xsd:dateTime)
bibo:doi	10.1101/2020.07.04.187989
bibo:pmid	32637958
has license	cc0
sha1sum (hex)	d7d2ae31c9b712dd4590da715cc68001b5c47300
schema:url	https://doi.org/10.1101/2020.07.04.187989
resource representing a document's title	A pH-dependent switch mediates conformational masking of SARS-CoV-2 spike
has PubMed Central identifier	PMC7337388
has PubMed identifier	32637958
schema:publication	bioRxiv
resource representing a document's body	covid:d7d2ae31c9b712dd4590da715cc68001b5c47300#body_text
is schema:about of	named entity 'enthalpy' named entity 'locks' named entity 'receptor' named entity 'endosomal' named entity 'locks' named entity 'dominated' named entity 'enthalpy' named entity 'pathogen' named entity 'based' named entity 'strain' named entity 'interactions' named entity 'unfolding' named entity 'sheds' named entity 'RBD' named entity 'partially' named entity 'vaccine' named entity 'unfolding' named entity 'spike' named entity 'physiological' named entity 'ACE2' named entity 'virus' named entity 'pathogen' named entity 'antibodies' named entity 'receptor binding' named entity 'enthalpy' named entity 'RBD' named entity 'ACE2' named entity 'antibodies' named entity 'SARS-CoV-2' named entity 'vaccine' named entity 'physiological' named entity 'SARS-CoV-2' named entity 'Ligand' named entity 'SARS-CoV-2' named entity 'bound states' named entity 'cryo-EM' named entity 'SARS-CoV-2' named entity 'Cryo-EM' named entity 'enthalpy' named entity 'ACE2' named entity 'molecular mechanism' named entity 'enthalpy' named entity 'enthalpy' named entity 'differential scanning calorimetry' named entity 'ACE2' named entity 'enthalpy' named entity '5.5' named entity 'CC0 license' named entity 'bioRxiv' named entity 'trimerization' named entity 'physiological pH' named entity 'peer review' named entity 'physiological pH' named entity 'endosomal' named entity 'atomic model' named entity '5.5' named entity 'CC0 license' named entity 'DSC'

Faceted Search & Find service v1.13.91 as of Mar 24 2020

Alternative Linked Data Documents: Sponger | ODE Content Formats:

RDF

ODATA

Microdata

About

OpenLink Virtuoso version 07.20.3229 as of Jul 10 2020, on Linux (x86_64-pc-linux-gnu), Single-Server Edition (94 GB total memory)
Data on this page belongs to its respective rights holders.
Virtuoso Faceted Browser Copyright © 2009-2025 OpenLink Software